The impact of chronic bupropion on plasma cotinine and on the subjective effects of ad lib smoking: a randomized controlled trial in unmotivated smokers.

Bupropion is an efficacious non-nicotine medication for smoking cessation; however, its cessation-mediating mechanism is unclear. This randomized, placebo-controlled trial examined the effect of bupropion SR (300 mg/day for 6 weeks) on plasma cotinine and on the subjective effects of smoking in 24 current daily smokers who were not trying to quit or reduce smoking. Subjective effects of smoking, as well as cue-elicited responses were assessed at bi-weekly experimental sessions using validated scales. Several indices of cigarette consumption were measured. Plasma cotinine decreased from 280 (+/-133) microg/l at baseline to 205 (+/-108) microg/l at end of treatment in the bupropion group (p=0.036), but no significant change was found in the placebo group. Daily cigarette count and puff topography did not significantly change in either group. In contrast to placebo, bupropion increased post-smoking satiety (p=0.045). Both groups reported higher craving (p=0.025) and withdrawal (p=0.014) after exposure to smoking-related pictures, compared to neutral pictures. This biased reactivity was not significantly affected by treatment condition (p>0.1). Therefore, bupropion does not appear to impact the smokers' response to conditioned smoking-related cues but influences the unconditioned subjective effects of smoking in unmotivated smokers. This study is among the first to systematically investigate the effect of chronic bupropion administration, free from the confounding effect of the smoker's motivation to quit smoking.

Sex differences in hormonal responses to a social stressor in chronic major depression.

BACKGROUND: Acute depression has been associated with increased hypothalamic-pituitary-adrenal (HPA) reactivity. While chronicity of depressive illness influences symptoms, course and outcome, its effect on the HPA axis has not been extensively evaluated. The current study evaluated cortisol stress responses to a social challenge in chronic major depressive disorder (CMDD). METHODS: Cortisol stress responses to the Trier Social Stress Test (TSST) were compared in 26 participants with CMDD and 28 healthy controls using repeated measures analysis of variance (RANOVA). In addition, group differences in area under the curve (AUC) and peak percentage change in cortisol were examined. RESULTS: The RANOVA indicated a significant sex by condition interaction in cortisol responses to the social challenge. Post-hoc testing of pair-wise group differences revealed that in females, CMDD subjects had greater cortisol levels in response to the TSST than did controls. Similarly, AUC was greater in females with CMDD than in female controls. Neither of these differences was significant in males. However, male CMDD subjects exhibited a significantly decreased peak percentage change in cortisol in response to the TSST than did male controls. CONCLUSIONS: Males and females with CMDD exhibited unique differences in cortisol responses to the social challenge relative to controls. In females, CMDD subjects had greater overall secretion of cortisol whereas in males, CMDD subjects had a blunted peak response to the social stressor. Sex differences are an important consideration in future work in this population.

Depression and the workplace: a progress report.

There has been considerable interest recently in the relationship between depression and the workplace. This interest is driven by the growing recognition that depressive disorders are highly prevalent in the workplace and have an enormously negative impact on performance, productivity, absenteeism, and disability costs. A variety of clinical research with occupational-related samples has helped to define those at risk for depression and has led to a better understanding of the overlap of the construct of clinical depression with more longstanding occupational health and organizational psychology models such as stress, burnout, and job satisfaction. From an employer perspective, depression's impact remains largely unmitigated due to stigma, uncertainty about treatment's cost effectiveness, and lack of effective interventions delivered in a workplace setting. Progress in these areas is reviewed with suggestions for future directions.

The interactive functioning of anxiety and depression in agonistic encounters and reconciliation.

This paper explores the well-known overlap of anxiety and depressive symptoms in mood and anxiety disorders. We suggest that the regulation of both negative and positive affects has served important adaptive functions (especially for coping with threats, losses, failures and defeats), and that in some contexts both affect systems require regulation at the same time (e.g. increased anxiety coupled with low positive affect). Here we will focus on how low positive and high negative affect in the individual experiencing losses and defeats regulates their competitive and acquisitive behaviors and in some cases may prevent, de-escalate, and possibly terminate on-going agonistic (hierarchical) encounters. When high negative affect (anxiety) and low positive affect (depression) fail to fulfill their adaptive roles, they tend to persist and often intensify. This may lead each affect control system to stimulate specific types of anxiety and depressive disorders, exhibiting features reminiscent of the original adaptive function of the behavior. Furthermore, as these different systems tend to operate in a synchronous fashion, the psychiatric syndromes they generate are often comorbid.

Usage and longitudinal effectiveness of a Web-based self-help cognitive behavioral therapy program for panic disorder.

BACKGROUND: Anxiety disorders are common problems that result in enormous suffering and economic costs. The efficacy of Web-based self-help approaches for anxiety disorders has been demonstrated in a number of controlled trials. However, there is little data regarding the patterns of use and effectiveness of freely available Web-based interventions outside the context of controlled trials. OBJECTIVE: To examine the use and longitudinal effectiveness of a freely available, 12-session, Web-based, cognitive behavioral therapy (CBT) program for panic disorder and agoraphobia. METHODS: Cumulative anonymous data were analyzed from 99695 users of the Panic Center. Usage statistics for the website were examined and a longitudinal survey of self-reported symptoms for people who registered for the CBT program was conducted. The primary outcome measures were self-reported panic-attack frequency and severity at the beginning of each session (sessions 2-12). RESULTS: Between September 1, 2002 and February 1, 2004, there were 484695 visits and 1148097 page views from 99695 users to the Panic Center. In that same time period, 1161 users registered for the CBT program. There was an extremely high attrition rate with only 12 (1.03%) out of 1161 of registered users completing the 12-week program. However, even for those who remained in the program less than 12 weeks we found statistically significant reductions (P<.002) in self-reported panic attack frequency and severity, comparing 2 weeks of data against data after 3, 6, or 8 weeks. For example, the 152 users completing only 3 sessions of the program reduced their average number of attacks per day from 1.03 (week 2) to 0.63 (week 3) (P<.001). CONCLUSIONS: Freely available Web-based self-help will likely be associated with high attrition. However, for the highly self-selected group who stayed in the program, significant improvements were observed.

A PET provocation study of generalized social phobia.

In an investigation of the neural circuits that may mediate the subjective experience of social phobia (SP), six male patients with a primary DSM-IV diagnosis of generalized social phobia watched, in the presence of a group of "communication experts," a videotape of themselves giving an impromptu talk (Exposure condition). In the control Baseline condition, they viewed a videotape of a socially competent stranger giving a talk. Regional cerebral blood flow was measured thrice under each condition. The study revealed significant deactivations from Baseline during Exposure in the right lingual gyrus (BA 18) and in the right medial frontal gyrus (BA 11); significant activations during Exposure were not observed. Deactivation of these regions may reflect a strategy of visual avoidance employed by the patients to dampen their phobic experience.

The 5-factor model of personality and antidepressant medication compliance.

OBJECTIVE: Medication noncompliance is a significant problem for effective pharmacologic treatment of major depressive disorder (MDD). Attempts to explore predictors of compliance have primarily focused on demographic characteristics; for the most part, these have been shown to be unrelated to compliance. Conversely, the relation between personality characteristics and compliance has been relatively understudied. The primary purpose of this study was to explore the relation between personality characteristics and compliance with antidepressant medication in patients with major depressive disorder (MDD). METHOD: Over 14 weeks, we evaluated a sample of outpatients (n = 65) who were receiving antidepressant treatment. We monitored compliance electronically, using the Medication Event Monitoring System. We assessed personality characteristics with the NEO Five-Factor Inventory-Revised. We also assessed depression severity and the frequency and severity of side effects. RESULTS: Extraversion was a significant negative predictor of compliance. This was largely explained by the relation between compliance and the Activity facet within Extraversion. We also found a negative relation between the Feelings facet and compliance, while the Modesty facet was a significant positive predictor of compliance with antidepressant medication. Neither severity of depression nor side effects predicted compliance. CONCLUSIONS: These results suggest that correlates of personality are important, although frequently ignored, predictors of compliance with antidepressant medication. Identifying predictors of medication compliance may help in the development of individualized treatment regimens and lead to improved therapeutic outcome in the treatment of MDD.

Hypnosis, memory, and frontal executive functioning.

According to the dissociated-control hypothesis forwarded by Woody and Bowers (1994), the effects of hypnosis are consistent with attenuated frontal lobe functioning. The present study was designed to compare the performance of participants with high and low hypnotic ability on a variety of memory tasks thought to be sensitive to frontal lobe functioning, as well as some control memory tasks not considered to be sensitive to such functioning. Results generally indicated that participants with high hypnotic ability have more difficulty with tasks sensitive to frontal lobe functioning, including free recall, proactive interference, and source amnesia tasks, both within and outside of the context of hypnosis. These differences, which were not found for nonfrontal tasks, are generally supportive of the dissociated control theory of hypnotic responding.

A Web-based screening instrument for depression and anxiety disorders in primary care.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders are common and result in considerable suffering and economic loss. People suffering from major depressive disorder and/or anxiety disorders are commonly encountered in the primary care setting. Unfortunately, most people with these disorders remain either untreated or inadequately treated; current data suggest that general practitioners fail to diagnose up to half of cases of major depressive disorder or anxiety. There is a need for screening tools that will help physicians and other professionals in primary care recognize and adequately treat major depressive disorder and anxiety disorders. While the currently-available self-report screening instruments have been demonstrated to be reliable and valid, there remain considerable barriers to their widespread use in primary care. OBJECTIVE: The purpose of the present study is to report preliminary validation data for a freely-available, brief, Web-based, self-report screener for major depressive disorder and anxiety disorders. METHODS: The Web-Based Depression and Anxiety Test (WB-DAT) was administered to 193 subjects who presented for assessment and/or treatment in ongoing research projects being conducted at the Mood and Anxiety Program and Clinical Research Department at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada. Subjects completed the Web-based screening instrument and were subsequently interviewed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) Axis I Disorders (SCID-I/P). The diagnostic data from the screening instrument were then compared with the data from the individual's SCID-I/P interview. Diagnostic concordance between SCID-I/P diagnoses and the Web-Based Depression and Anxiety Test were assessed using Cohen's kappa, sensitivity, specificity, positive predictive value, negative predictive value, and efficiency. RESULTS: Agreement ranged from acceptable to good (0.57-0.70) for major depressive disorder, panic disorder with and without agoraphobia (PD+/-AG), social phobia/social anxiety disorder, obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), and post traumatic stress disorder (PTSD). With the exception of generalized anxiety disorder, the sensitivity (0.71-0.95) and specificity (0.87-0.97) for the major diagnostic categories assessed by the Web-Based Depression and Anxiety Test were good. The sensitivity for generalized anxiety disorder was somewhat lower (0.63) but acceptable. Positive predictive values were good (0.60-0.75) for major depressive disorder, obsessive compulsive disorder, generalized anxiety disorder, and post traumatic stress disorder, and acceptable for panic disorder with and without agoraphobia and for social phobia/social anxiety disorder. CONCLUSIONS: These preliminary data suggest that the Web-Based Depression and Anxiety Test is reliable for identifying patients with and without major depressive disorder and the anxiety disorders of panic disorder with and without agoraphobia, social phobia/social anxiety disorder, obsessive compulsive disorder, and post traumatic stress disorder. Further research is required in a larger sample in primary care.

The impact of anxiety disorders on educational achievement.

Anxiety disorders typically have an age of onset in childhood and adolescence, resulting in significant disability in social and occupational functioning. Epidemiological evidence suggests that persons with psychiatric disorders and perhaps especially social phobia are at increased risk for premature withdrawal from school [Am. J. Psychiatry 157 (2000) 1606]. In order to further determine the impact of anxiety disorders on school functioning and/or premature withdrawal from school, 201 patients meeting DSM-IV criteria for a primary anxiety disorder completed a school leaving questionnaire as well as self-report measures of anxiety, depression, and social adjustment. About 49% (n = 98) reported leaving school prematurely and 24% of those indicated that anxiety was the primary reason for this decision. Patients who had left school prematurely were significantly more likely to have a lifetime diagnosis of generalized social phobia, a past history of alcohol abuse/dependence and a greater number of lifetime diagnoses than those who completed their desired level of education. This study suggests that anxiety disorders, and perhaps especially generalized social phobia, are associated with premature withdrawal from school. Further studies are required to determine methods for early identification and treatment of anxiety disorders in school aged children to enable these students to reach their full potential.

Quality of life and the anxiety disorders.

Quality of life (QoL) is a concept that has become increasingly used in mental health care. Recent studies have compared the impact of different anxiety disorders on different domains of QoL; however, instruments generally used to assess QoL in this population have varying specificity, considerable redundancy, and occasionally inappropriate content. Three hundred and sixty consecutive admissions to an anxiety disorders clinic were assessed. Participants and clinicians completed a number of QoL measures. Results indicated that impairment measures designed for use with anxiety-disordered samples in fact assess only occupational functioning and relationships and activities outside of occupation, and that individuals with Social Phobia (SP) were more impaired on the latter than those with Panic Disorder (PD). Furthermore, only Social Phobia accounted for unique variance in the three Medical Outcome Study Health Survey (MOS) subscales relevant to quality of life. Of the MOS subscales relevant to symptoms, mood regulation, physical functioning, and pain were associated with compromised overall QoL.

Learning needs of patients with congestive heart failure.

BACKGROUND: It is suggested that more effective and efficient educational intervention can be created by matching the program to patient learning needs. Previous attempts to determine the learning needs of patients with congestive heart failure (CHF) find all types of information endorsed as very important to learn. OBJECTIVES: To increase differentiation between patients' ratings of information needs by modifying the CHF Patient Learning Needs Inventory (CHFPLNI) and examined predictors of learning needs. METHODS: Thirty-four inpatients with CHF from the Toronto General Hospital, Toronto, Ontario completed the modified CHFPLNI and rank ordered the perceived importance of eight categories of CHF knowledge measured by the CHFPLNI. Patients also completed measures of emotional distress, fatigue, health beliefs, locus of control and current CHF knowledge. RESULTS: Ratings across all information categories were similar (M=4.4-5.3/7) and highly correlated (r=0.52-0.87). Patients indicated information on medication, cardiovascular anatomy and physiology, and treatment were the most important to learn on both the CHFPLNI and by rank ordering. Higher fatigue was correlated with information needs on diet (r=0.37), activity (r=0.37), psychological (r=0.38) and risk (r=0.37) factors. No other variables consistently predicted learning needs. CONCLUSIONS: Changing the format of the CHFPLNI did not increase the differentiation of patients' ratings across information categories. The assessment of patients' learning needs using extensive questionnaires does not appear warranted because simple rank ordering obtained similar information. Individuals who are more fatigued wanted more information on those aspects of care that they managed on a day-to-day basis.

A confirmatory factor analysis of a self-report version of the Liebowitz Social Anxiety Scale.

One of the most popular measures of social phobia is the Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987). The LSAS is a 24-item semi-structured interview measure of fear and avoidance experienced in a range of social and performance situations. Recently, the LSAS has been modified to a self-report version (LSAS-SR) by several independent groups (Cox, Ross, Swinson, & Direnfeld, 1998; Fresco et al., 2001; Mancini, Van Ameringen, & Oakman, 1999). A self-report version offers ease of administration, but it may differ from the structured interview version in its psychometric properties. We conducted confirmatory factor analyses of the self-report version of the LSAS using data from a sample of 188 outpatients with anxiety disorders. The structure and psychometric properties of the LSAS-SR are highly similar to that of the LSAS and robust across groups of patients with a variety of primary anxiety disorders. We argue in favor of adopting the 4-factor model for the LSAS proposed by Safren et al. (1999) instead of the models implied by the scoring instructions for the LSAS.

Does SSRI augmentation with antidepressants that influence noradrenergic function resolve depression in obsessive-compulsive disorder?

BACKGROUND: Obsessive compulsive disorder (OCD) often coexists with major depressive disorder (MDD). Serotonergic antidepressant medications have emerged as the treatment of choice for both OCD and MDD. In the usual course of events, both the patient's OCD and depressive symptoms improve in parallel following initiation of serotonin reuptake inhibitor (SRI) treatment for OCD. However, such is not always the case. We report here on a series of ten patients whose OCD but not depression improved following a trial of SRI therapy. METHOD: Ten patients with OCD and comorbid MDD who experienced a worsening or exacerbation of depressive symptoms while being maintained on an adequate dose of SRI therapy were treated using a combination of SRIs and agents with effects on noradrenergic reuptake. Response to treatment was based on clinician-ratings of severity and improvement of OCD and MDD (CGI-S and CGI-I). RESULTS: Following augmentation, nine of the ten patients had a significant improvement/resolution of their MDD, with little further change in the severity of their OCD. LIMITATIONS: Inferences from the results of this study are limited by the lack of a control group, the small sample size, and the use of nonstandardized ratings as measures of symptom severity. CONCLUSIONS: These results are of practical significance to clinicians insofar as they suggest a possible guideline to clinicians treating depression in OCD with SSRIs without success.